The matching of alveolar ventilation to perfusion in the lung is critical for efficient gas exchange. This project is to sort out three mechanisms that may affect distribution of regional blood flow in lung: regional differences in vascular architecture or mechanics, regional differences in hydrostatic perfusion pressure and regional differences in lung expansion. Studies will be done suing isolated perfused dog lungs, isolated lungs fixed for examination by microscopy, and intact dogs. In isolated lungs, vascular pressure vs flow relationships in small pieces of lung parenchyma will be generated using radioactively labeled microspheres to measure regional flows. Effects of varying regional vascular pressure and regional lung volume will be studied, and a correlation of shapes of regional perfusion pressure vs flow curves with anatomical position will be investigated. Using data from these detailed studies of regional vascular mechanics, mathematical modeling will be done to generate predictions to be tested in vivo. Perfusion-fixed tissue will be examined using quantitative morphometry to detect regional differences in vascular architecture in an effort to find a mechanism for regional differences in perfusion pressure vs flow curves. A study of regional differences in solute exchange in isolated lungs will also be undertaken to complete this description of regional differences in pulmonary vascular function.